Neuronal intranuclear inclusion disease (NIID), caused by a GGC repeat expansion in the 5′-untranslated region of NOTCH2NLC, is a rare cause of adult-onset leukoencephalopathy. It is characterised by highly variable clinical manifestations, MRI evidence of leukoencephalopathy with diffusion-weighted imaging (DWI) high signal at the corticomedullary junction, and eosinophilic intranuclear inclusions on histopathology. In recent years, the number of reported cases has exponentially increased in China, Japan and Taiwan. Of the limited number of reported European cases with pathologically confirmed NIID, only two harboured the same GGC repeat expansion. NIID has never previously been described in New Zealand (NZ). 

Patients were screened for NOTCH2NLC GGC repeat expansion using fragment analysis and repeat-primed PCR.

Heterozygous NOTCH2NLC GCC repeat expansions were found in four patients, 3 NZ Maori and one Cook Island Maori, 2 women and 2 men.  All were unrelated. Age at symptom onset ranged between 18 and 61 years. Three presented with relapsing encephalopathy and one with an acute brainstem syndrome. Other clinical manifestations included: cognitive impairment (4/4), ataxia (4/4), autonomic dysfunction (3/4), neuropsychiatric symptoms (3/4), headache (3/4), rod-cone retinal dystrophy (2/4), cough (2/4), muscle weakness (2/4) and seizures (2/4). All had extensive leukoencephalopathy and DWI high signal at the corticomedullary junction. In addition, 2/4 had paravermis involvement. On electrodiagnostics, there was sensory and/or motor conduction velocity slowing in 3/4 patients. Of the three that underwent skin biopsy, all had eosinophilic intranuclear inclusions. 

This is the first description of NIID in NZ. Of significance, all had Polynesian ancestry. Archaeological, linguistic and anthropological sources suggest Polynesian migration originated from East Asia, particularly Taiwan. This raises the potential for a founder effect. Further work is being done to identify cases of unrecognised NIID in NZ.